2022
Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine model
2021
DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model
Paluri SL, Burak M, Senejani AG, Levinson M, Rahim T, Clairmont K, Kashgarian M, Alvarado-Cruz I, Meas R, Cardó-Vila M, Zeiss C, Maher S, Bothwell ALM, Coskun E, Kant M, Jaruga P, Dizdaroglu M, Lloyd R, Sweasy JB. DNA glycosylase deficiency leads to decreased severity of lupus in the Polb-Y265C mouse model. DNA Repair 2021, 105: 103152. PMID: 34186496, PMCID: PMC8635285, DOI: 10.1016/j.dnarep.2021.103152.Peer-Reviewed Original Research
2020
B cell-intrinsic TLR9 expression is protective in murine lupus
Tilstra JS, John S, Gordon RA, Leibler C, Kashgarian M, Bastacky S, Nickerson KM, Shlomchik MJ. B cell-intrinsic TLR9 expression is protective in murine lupus. Journal Of Clinical Investigation 2020, 130: 3172-3187. PMID: 32191633, PMCID: PMC7260024, DOI: 10.1172/jci132328.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Systemic lupus erythematosusTLR9 deficiencyTLR9 expressionDendritic cellsB cellsPlasmacytoid dendritic cellsAnti-nucleosome antibodiesLupus erythematosusAutoantibody productionMurine lupusSLE pathogenesisTLR9 signalsReceptor 9Cell type-specific effectsType-specific effectsDisease pathogenesisTherapeutic potentialSelective deletionDiseaseNonredundant roleNephritisLupusPathogenesisDeficiency
2011
A Small-Molecule Macrophage Migration Inhibitory Factor Antagonist Protects against Glomerulonephritis in Lupus-Prone NZB/NZW F1 and MRL/lpr Mice
Leng L, Chen L, Fan J, Greven D, Arjona A, Du X, Austin D, Kashgarian M, Yin Z, Huang XR, Lan HY, Lolis E, Nikolic-Paterson D, Bucala R. A Small-Molecule Macrophage Migration Inhibitory Factor Antagonist Protects against Glomerulonephritis in Lupus-Prone NZB/NZW F1 and MRL/lpr Mice. The Journal Of Immunology 2011, 186: 527-538. PMID: 21106847, PMCID: PMC3124407, DOI: 10.4049/jimmunol.1001767.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell Migration InhibitionFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGlomerulonephritisHumansIntramolecular OxidoreductasesIsoxazolesLupus Erythematosus, SystemicMacrophage Migration-Inhibitory FactorsMiceMice, Inbred MRL lprMice, Inbred NZBMice, KnockoutMolecular Sequence DataRandom AllocationReceptors, ImmunologicConceptsMacrophage migration inhibitory factorMRL/lpr miceNZB/NZW F1Systemic lupus erythematosusMigration inhibitory factorLupus erythematosusLpr miceDihydro-5-isoxazole acetic acid methyl esterHigh-expression MIF allelesInhibitory factorExcessive proinflammatory responsesRetention of monocytesEnd-organ injuryEnd-organ damageProinflammatory cytokine productionDifferent autoimmune diseasesB cell activationMIF antagonismMIF antagonistAutoantibody productionChemokine expressionProinflammatory cytokinesAutoimmune diseasesCytokine productionMIF alleles
2010
Dendritic Cells in Lupus Are Not Required for Activation of T and B Cells but Promote Their Expansion, Resulting in Tissue Damage
Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ. Dendritic Cells in Lupus Are Not Required for Activation of T and B Cells but Promote Their Expansion, Resulting in Tissue Damage. Immunity 2010, 33: 967-978. PMID: 21167752, PMCID: PMC3010763, DOI: 10.1016/j.immuni.2010.11.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesBlood Component RemovalB-LymphocytesCell DifferentiationCell MovementDendritic CellsDisease Models, AnimalHumansImmunoglobulin Class SwitchingInterferon-gammaLupus Erythematosus, SystemicLymphocyte ActivationMiceMice, Inbred C57BLMice, Inbred MRL lprT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsDendritic cellsAdaptive immune responsesMurine lupusImmune responseAbsence of DCsEffects of DCsSystemic lupus erythematosusSerum immunoglobulin concentrationsPotential therapeutic targetLupus erythematosusInterstitial infiltratesAutoimmune disordersHumoral responseAutoantibody concentrationsPlasmablast numbersImmunoglobulin concentrationsTherapeutic targetB cellsTissue damageLupusCell numberCellsInitial activationComplex roleActivationThe maximal cytoprotective function of the heat shock protein 27 is dependent on heat shock protein 70
Sreedharan R, Riordan M, Thullin G, Van Why S, Siegel NJ, Kashgarian M. The maximal cytoprotective function of the heat shock protein 27 is dependent on heat shock protein 70. Biochimica Et Biophysica Acta 2010, 1813: 129-135. PMID: 20934464, PMCID: PMC3014454, DOI: 10.1016/j.bbamcr.2010.08.012.Peer-Reviewed Original ResearchConceptsHeat shock protein 70Shock protein 70Cell injuryProtein 70Heat shock protein 27Renal cell injuryExpression of HSP27Maximal cytoprotective effectShock protein 27Endogenous hspNuclear binding sitesCytoprotective effectsInjuryRenal cellsLLC-PK1 cellsProtein 27Specific siRNAHSP-70HSP70 inductionRespective controlsHSP27Particular HSP70Cytoprotective functionEnergy depletionATP depletionAltered renal proximal tubular endocytosis and histology in mice lacking myosin‐VI
Gotoh N, Yan Q, Du Z, Biemesderfer D, Kashgarian M, Mooseker MS, Wang T. Altered renal proximal tubular endocytosis and histology in mice lacking myosin‐VI. Cytoskeleton 2010, 67: 178-192. PMID: 20175219, PMCID: PMC3468331, DOI: 10.1002/cm.20435.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsApoptosis Regulatory ProteinsCell TransdifferentiationEndocytosisHorseradish PeroxidaseKidney Tubules, ProximalLow Density Lipoprotein Receptor-Related Protein-2MiceMice, Neurologic MutantsMicrofilament ProteinsMicrovilliMyosin Heavy ChainsVesicular Transport ProteinsConceptsProximal tubule cellsAlbumin excretionSv miceTubule cellsProximal tubule brush borderGlomerular flow rateProximal tubular dilationUrinary albumin excretionElevated blood pressureReduced body weightProximal tubular endocytosisRenal proximal tubule brush borderTubule brush borderProximal tubular uptakeBlood acid-base parametersMouse kidney proximal tubulesKidney proximal tubulesBlood pressureUrine volumeUrinary excretionAcid-base parametersRenal homogenatesTubular dilationPlasma concentrationsRenal clearance
2008
Disruption of Myosin 1e Promotes Podocyte Injury
Krendel M, Kim SV, Willinger T, Wang T, Kashgarian M, Flavell RA, Mooseker MS. Disruption of Myosin 1e Promotes Podocyte Injury. Journal Of The American Society Of Nephrology 2008, 20: 86-94. PMID: 19005011, PMCID: PMC2615733, DOI: 10.1681/asn.2007111172.Peer-Reviewed Original ResearchConceptsChronic renal injuryNormal glomerular filtrationGlomerular basement membraneRenal injuryKidney inflammationPodocyte foot processesGlomerular diseasePodocyte injuryGlomerular filtrationRenal tissueFoot processesPodocyte functionBasement membraneInjuryUltrastructural levelDiseaseMiceType IProteinuriaInflammationKidneyImportant rolePodocytes
2005
HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells
Riordan M, Sreedharan R, Wang S, Thulin G, Mann A, Stankewich M, Van Why S, Kashgarian M, Siegel NJ. HSP70 binding modulates detachment of Na-K-ATPase following energy deprivation in renal epithelial cells. American Journal Of Physiology. Renal Physiology 2005, 288: f1236-f1242. PMID: 15701813, DOI: 10.1152/ajprenal.00438.2004.Peer-Reviewed Original ResearchConceptsRenal epithelial cellsATP depletionMolecular chaperone Hsp70Binding of Hsp70Na-K-ATPaseFundamental cellular mechanismsRenal epithelial polarityCultured renal epithelial cellsEpithelial cellsHeat shock protein 70Protein clathrinEpithelial polarityMolecular chaperonesOverexpression of HSP70Chaperone Hsp70Shock protein 70Energy deprivationLLC-PK1 cellsStress proteinsMolecular mechanismsHSP bindingHSP70Cell lysatesCellular mechanismsATP turnover
2001
K+-induced HSP-72 expression is mediated via rapid Ca2+ influx in renal epithelial cells
Eickelberg O, Geibel J, Seebach F, Giebisch G, Kashgarian M. K+-induced HSP-72 expression is mediated via rapid Ca2+ influx in renal epithelial cells. American Journal Of Physiology. Renal Physiology 2001, 281: f280-f287. PMID: 11457719, DOI: 10.1152/ajprenal.2001.281.2.f280.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalcium Channel BlockersCell LineDiltiazemEgtazic AcidEnzyme InhibitorsEpithelial CellsGallic AcidGenes, ReporterHeat-Shock ProteinsHSP72 Heat-Shock ProteinsImmunoblottingKidney Tubules, ProximalMicroscopy, ConfocalPotassiumPromoter Regions, GeneticRecombinant Fusion ProteinsSodiumSwineThapsigarginUrotheliumConceptsHSP 72 expressionPromoter activityHSP 72Protein expressionProtective cellular responseLuciferase reporter geneHSP-25Heat shock protein expressionRenal epithelial cellsTranscriptional inductionShock protein expressionIonic stressReporter geneHSP-90 levelsHSC 73Cellular responsesChannel blocker diltiazemIntracellular lumenWestern blot analysisChelator EGTA-AMPathophysiological stimuliBlot analysisConfocal microscopyProtein levelsExtracellular space
2000
Regulation of DRA and AE1 in rat colon by dietary Na depletion
Rajendran V, Black J, Ardito T, Sangan P, Alper S, Schweinfest C, Kashgarian M, Binder H. Regulation of DRA and AE1 in rat colon by dietary Na depletion. AJP Gastrointestinal And Liver Physiology 2000, 279: g931-g942. PMID: 11052990, DOI: 10.1152/ajpgi.2000.279.5.g931.Peer-Reviewed Original ResearchIn vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse
Schechner J, Nath A, Zheng L, Kluger M, Hughes C, Sierra-Honigmann M, Lorber M, Tellides G, Kashgarian M, Bothwell A, Pober J. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9191-9196. PMID: 10890921, PMCID: PMC16844, DOI: 10.1073/pnas.150242297.Peer-Reviewed Original Research
1999
Thresholds for cellular disruption and activation of the stress response in renal epithelia
van Why S, Kim S, Geibel J, Seebach F, Kashgarian M, Siegel N. Thresholds for cellular disruption and activation of the stress response in renal epithelia. American Journal Of Physiology 1999, 277: f227-f234. PMID: 10444577, DOI: 10.1152/ajprenal.1999.277.2.f227.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCalciumCysteine EndopeptidasesDetergentsDifferential ThresholdDNA-Binding ProteinsEpithelial CellsHeat Shock Transcription FactorsHeat-Shock ProteinsIntracellular MembranesKidneyL-Lactate DehydrogenaseLLC-PK1 CellsMultienzyme ComplexesOctoxynolProteasome Endopeptidase ComplexSodium-Potassium-Exchanging ATPaseSolubilityStress, PhysiologicalSwineTranscription FactorsConceptsATP depletionRenal epitheliumLactate dehydrogenase releaseCellular ATPReduction of ATPRenal ischemiaIntracellular calciumActivation of HSF1Heat shock transcription factorDehydrogenase releaseControl ATPStress responseControl levelsProgressive accumulationProteasome inhibitionAdaptive inductionHSF activationRapid fallActivationEpitheliumIncremental increaseCellular disruptionResponseATPIschemiaColonic H-K-ATPase β-subunit: identification in apical membranes and regulation by dietary K depletion
Sangan P, Kolla S, Rajendran V, Kashgarian M, Binder H. Colonic H-K-ATPase β-subunit: identification in apical membranes and regulation by dietary K depletion. American Journal Of Physiology 1999, 276: c350-c360. PMID: 9950762, DOI: 10.1152/ajpcell.1999.276.2.c350.Peer-Reviewed Original ResearchDifferential regulation of NHE isoforms by sodium depletion in proximal and distal segments of rat colon
Ikuma M, Kashgarian M, Binder H, Rajendran V. Differential regulation of NHE isoforms by sodium depletion in proximal and distal segments of rat colon. American Journal Of Physiology 1999, 276: g539-g549. PMID: 9950829, DOI: 10.1152/ajpgi.1999.276.2.g539.Peer-Reviewed Original ResearchConceptsDietary sodium depletionSodium depletionDistal colonRat colonProtein expressionMRNA abundanceBlot analysisDose-dependent inhibitorApical membrane vesiclesElectroneutral NaCl absorptionWestern blot analysisDifferential regulationNormal ratsProximal colonHOE 694Multiple diverse effectsColonDistal segmentsNaCl absorptionNHE isoformsExchange activityExchanger isoformsNorthern blot analysisDifferential effectsPretranslational level
1998
Role of heat stress response in the tolerance of immature renal tubules to anoxia
Gaudio K, Thulin G, Mann A, Kashgarian M, Siegel N. Role of heat stress response in the tolerance of immature renal tubules to anoxia. American Journal Of Physiology 1998, 274: f1029-f1036. PMID: 9841493, DOI: 10.1152/ajprenal.1998.274.6.f1029.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornBlotting, NorthernCarbonyl Cyanide m-Chlorophenyl HydrazoneCell HypoxiaDNA, MitochondrialDNA-Binding ProteinsElectrophoresisHeat Shock Transcription FactorsHeat-Shock ProteinsHot TemperatureHSP72 Heat-Shock ProteinsKidney TubulesMitochondriaNystatinOuabainOxygen ConsumptionRatsRNA, MessengerTranscription FactorsAntibodies against mesangial cells and their secretory products in chronic renal allograft rejection in the rat.
Paul L, Muralidharan J, Muzaffar S, Manting E, Valentin J, de Heer E, Kashgarian M. Antibodies against mesangial cells and their secretory products in chronic renal allograft rejection in the rat. American Journal Of Pathology 1998, 152: 1209-23. PMID: 9588890, PMCID: PMC1858589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoantigensBasement MembraneBiglycanBlotting, WesternCells, CulturedChronic DiseaseDecorinEndothelium, VascularExtracellular Matrix ProteinsFlow CytometryFluorescent Antibody Technique, IndirectGlomerular MesangiumGraft RejectionKidney TransplantationMaleProteoglycansRatsRats, Inbred F344Rats, Inbred LewTransplantation, HomologousConceptsMesangial cell culture supernatantsChronic renal allograft rejectionRenal allograft rejectionMesangial cellsChronic rejectionAllograft rejectionCell culture supernatantsChronic renal transplant rejectionFlow cytometryWestern blotEndothelial cellsGlomerular basement membrane antigenPost-transplant seraRenal transplant rejectionCell-mediated immunityPost-immunization seraPresence of antibodiesMesangial cell surfaceStrong autoantibody responseCulture supernatantsCultured mesangial cellsIndirect immunofluorescent studiesBasement membrane antigensIndirect immunofluorescent stainingTissue repair processATP releases HSP-72 from protein aggregates after renal ischemia
Aufricht C, Lu E, Thulin G, Kashgarian M, Siegel N, Van Why S. ATP releases HSP-72 from protein aggregates after renal ischemia. American Journal Of Physiology 1998, 274: f268-f274. PMID: 9486221, DOI: 10.1152/ajprenal.1998.274.2.f268.Peer-Reviewed Original ResearchHeat-shock protein 25 induction and redistribution during actin reorganization after renal ischemia
Aufricht C, Ardito T, Thulin G, Kashgarian M, Siegel N, Van Why S. Heat-shock protein 25 induction and redistribution during actin reorganization after renal ischemia. American Journal Of Physiology 1998, 274: f215-f222. PMID: 9458842, DOI: 10.1152/ajprenal.1998.274.1.f215.Peer-Reviewed Original ResearchConceptsHSP-25Renal ischemiaHeat shock protein 25Ischemic renal injuryH reflowRat renal cortexControl proximal tubulesRenal injuryPostischemic recoveryRenal cortexIschemiaProximal tubulesIntracytoplasmic accumulationPeak levelsHeat shock proteinsProtein 25Actin stainingInsoluble cytoskeletal fractionPunctate accumulationsCytoskeletal disruptionSmall heat shock proteinsRegulatory roleInductionIntracellular distributionCytoskeletal fractionAre there New Activity Markers of Glomerular Inflammation? A Renal Pathologist's View
Kashgarian M. Are there New Activity Markers of Glomerular Inflammation? A Renal Pathologist's View. Kidney & Blood Pressure Research 1998, 21: 215-216. PMID: 9762837, DOI: 10.1159/000025858.Peer-Reviewed Original Research